Premenstrual symptoms interference and equol production status in Japanese collegiate athletes: A cross-sectional study.

AIM: Consumption of soy isoflavones reduces the risk of estrogen-related diseases, such as menopausal symptoms, osteoporosis, and cardiovascular disease. Equol is metabolized from the isoflavone daidzein by intestinal bacteria and has higher bioavailability than other isoflavones. Equol producers are believed to benefit from soybean consumption to a greater extent than non-producers. Recently, we showed that equol non-producers were at significant risk of premenstrual syndrome (PMS). Previously, we reported that PMS is a common menstrual problem in female athletes, and almost half of the studied athletes felt a negative effect of premenstrual symptoms on their athletic performance. This study was conducted to evaluate the relation between PMS and equol production status in Japanese collegiate athletes. METHODS: This was a cross-sectional, observational study that included 88 Japanese female collegiate athletes. Equol production status was determined using urine samples collected after a soy challenge test. The subjects also completed a questionnaire about their premenstrual symptoms and their competitive career. RESULTS: The prevalence of equol producers was 29.5% in Japanese collegiate athletes. The athletic performance of 54.5% of athletes was found to suffer in competition or in practice due to premenstrual symptoms. In multivariate analysis, equol non-producers (odds ratio, 3.34; 95% confidence interval, 1.03-12.20) and restriction of bodyweight (odds ratio, 4.94; 95% confidence interval, 1.47-20.00) were shown to be significant risk factors for poor athletic performance. CONCLUSION: This study showed a relation between athletic performance and equol production status in Japanese collegiate athletes.

Relationship of equol production between children aged 5-7 years and their mothers.

PURPOSE: The factors responsible for the production of isoflavone metabolites have not yet been identified. We aimed to examine the relationships of equol production between mother and child in a birth cohort in Japan. METHODS: Subjects were a part of the participants in a longitudinal study on pregnant women and their offspring. When children were 5-7 years old, mothers and children were asked to reply to a questionnaire on lifestyles and a 3-day child's dietary record. Mothers and children were given a bar-shaped soy snack (Soyjoy®) daily on two consecutive days (soy challenge). The snack contained 14 mg of overall soy isoflavones as the sum of aglycones and the glucosides for mothers and 7.5 mg for children. On the morning of day 0 and 3, they were asked to mail their first-void urines. Urinary isoflavone metabolites of 159 mother-child pairs were measured by a high-performance liquid chromatography method. RESULTS: Equol producers were 35.5 % among mothers and 13.8 % among children. Equol producer status of a child was neither associated with dietary intake nor with urinary levels of daidzein and genistein. After multiple adjustments for potential confounders, the estimated relative risk of equol producer was 2.75 (95 % confidence interval 1.00, 7.52) among children whose mother was an equol producer, compared with children whose mother was a non-producer. CONCLUSION: Child's equol production was associated with the mother's equol producer status. The effects of maternal factors on child's equol production should be studied further.

Relation between premenstrual syndrome and equol-production status.

AIM: Consumption of isoflavones, which are predominantly derived from soybeans, reduces the risk of estrogen-related diseases, such as menopausal symptoms, breast cancer, osteoporosis, and cardiovascular disease. Equol is more bioavailable than other soy isoflavones, and equol producers are believed to benefit to a greater extent. This study was conducted to evaluate the relation between premenstrual syndrome (PMS) and equol-production status in Japanese reproductive-age women. METHODS: This was a cross-sectional, observational study. The study included 144 Japanese women aged 20-45 years. PMS patients (n = 46) were recruited at three obstetrics and gynecology clinics. Control group women (n = 98) who were not receiving therapy for PMS were recruited from the local area by advertisement. The participants' equol-production status was determined using urine samples collected after a soy challenge test. RESULTS: The prevalence of equol producers was 41.8% in the control group and 23.9% in the patient group (P = 0.042). Using univariate analysis, significant risk factors for equol non-producers were being a PMS patient and being younger. In multivariate analysis with a step-wise model, being a PMS patient (odds ratio, 2.342; 95% confidence interval, 1.021-5.698) was shown to be a significant risk factor for being an equol non-producer. CONCLUSION: This study showed a relation between PMS and equol-production status in Japanese women.

Estrogen stimuli promote osteoblastic differentiation via the subtilisin-like proprotein convertase PACE4 in MC3T3-E1 cells.

Estrogenic compounds include endogenous estrogens such as estradiol as well as soybean isoflavones, such as daidzein and its metabolite equol, which are known phytoestrogens that prevent osteoporosis in postmenopausal women. Indeed, mineralization of MC3T3-E1 cells, a murine osteoblastic cell line, was significantly decreased in medium containing fetal bovine serum treated with charcoal-dextran to deplete endogenous estrogens, but estradiol and these soybean isoflavones dose-dependently restored the differentiation of MC3T3-E1 cells; equol was tenfold more effective than daidzein. These differentiation-promoting effects were inhibited by the addition of fulvestrant, which is a selective downregulator of estrogen receptors. Analysis of the expression pattern of bone-related genes by reverse transcription PCR (RT-PCR)/quantitative real-time PCR (qRT-PCR), which focused on responsiveness to the estrogen stimuli, revealed that the transcription of PACE4, a subtilisin-like proprotein convertase, was tightly linked with the differentiation of MC3T3-E1 cells induced by estrogen stimuli. Moreover, treatment with RNAi of PACE4 in MC3T3-E1 cells resulted in a drastic decrease of mineralization in the presence of estrogen stimuli. These results strongly suggest that PACE4 participates in bone formation at least in osteoblast differentiation, and estrogen receptor-mediated stimuli induce osteoblast differentiation through the upregulation of PACE4 expression.

Effects of natural S-equol supplements on overweight or obesity and metabolic syndrome in the Japanese, based on sex and equol status.

OBJECTIVES: Epidemiologic studies indicate that soy intake has an important role in the prevention of age-related health problems. Daidzein, the principal isoflavone contained in soy, is converted to S-equol by the intestinal bacteria. Not all individuals, however, can produce S-equol, which is considered the most biologically active metabolite. We studied the effects of a natural S-equol supplement on metabolic parameters associated with overweight or obesity and metabolic syndrome. METHODS: The study was a randomized, double-blinded, placebo-controlled, crossover design with no washout period. All subjects were considered overweight or obese if they had a body mass index ≥ 25 kg/m(2) . Placebo or natural S-equol tablets containing 10 mg S-equol were orally ingested each day for 12 weeks. A total of 54 Japanese overweight or obese outpatients were enrolled. The equol phenotype was determined, and various metabolic parameters, including cardio-ankle vascular index (CAVI), were measured. RESULTS: Equol non-producers comprised 67.9% of the overweight or obese subjects. The ratio of equol non-producers in this overweight or obese subject group was higher than the previously reported ratio of equol non-producers (approximately 50%) in the general population. Compared with the placebo group, intervention with natural S-equol led to a significant decrease in HbA1c, serum low-density lipoprotein cholesterol (LDL-C) levels and CAVI score. Furthermore, the effect was more prominent in the subgroup of female equol non-producers. CONCLUSION: The ratio of equol non-producers in overweight or obese populations might be higher than generally reported. Natural S-equol might have a role in glycaemic control and in the prevention of cardiovascular disease by its effects to lower LDL-C levels and CAVI scores in overweight or obese individuals.

Isolation and characterization of novel S-equol-producing bacteria from brines of stinky tofu, a traditional fermented soy food in Taiwan.

Six strains capable of transforming daidzein to S-equol were isolated from the fermented brines of stinky tofu purchased in Taiwan. Daidzein was completely converted into S-equol within 24h of incubation in five strains. All the strains were gram-positive, rod-shaped, obligately anaerobic, non-motile, and non-spore-forming. In a phylogenetic analysis based on 16S rRNA gene sequences, the strains distributed into three groups in the family Coriobacteriaceae. SNR40-432 (Group I) showed 98.6% 16S rRNA gene similarity and 48-49% DNA-DNA relatedness with Paraeggerthella hongkongensis HKU10(T), suggesting the possibility that SNR40-432 represents a new species in the genus Paraeggerthella. SNR48-44 (Group II) and SNR44-10, SNR45-571, SNR46-41, SNR48-350 (Group III) showed a maximum of 92.2 and 92.1% 16S rRNA gene similarities with Eggerthella sinensis HKU14(T) and Eggerthella lenta JCM9979(T), respectively, which denotes that each group may represent a novel genus and species in the family Coriobacteriaceae. This is the first report isolating equol-producing bacteria from food.

Effect of γ-tocopherol supplementation on premenstrual symptoms and natriuresis: a randomized, double-blind, placebo-controlled study.

BACKGROUND: This randomized, double-blind, placebo-controlled study aimed to investigate the effects of γ-tocopherol (Toc) supplementation on premenstrual symptoms and natriuresis. METHODS: We enrolled 51 Japanese women with premenstrual symptoms, particularly those who showed increased symptoms induced by water retention during the luteal phase compared with the follicular phase. Premenstrual symptoms were recorded in the first cycle's postmenstrual follicular phase; physical measurements and urine collection were conducted during the 48-h run-in period. The test supplement, which contained 180 mg of γ-Toc or placebo, was orally administered twice a day for 7 days during the luteal phase of the first and second cycles in a crossover manner. The same evaluation was conducted during the luteal phase, beginning in the morning of the sixth day of supplement administration. RESULTS: Compared with placebo intake, γ-Toc intake significantly reduced "fatigue" and "irritability/anger" symptoms. Furthermore, compared with placebo intake, γ-Toc intake significantly reduced the thigh circumference. Regarding the "swelling of the legs" and "heavy legs" symptoms and the thigh circumference, the biphasic trend of increasing and decreasing values in the daytime and morning, respectively, during the follicular phase was not observed at the luteal phase with placebo intake. Contrastingly, γ-Toc intake resulted in significantly lower values in the morning than placebo intake. The mean difference in 24-h urinary sodium excretion between γ-Toc and placebo intake was 10.6 mEq (95% confidence interval (CI): -0.1, 21.4, p = 0.05, power 55%). Plasma γ-Toc and its metabolite γ-carboxyethyl hydroxychroman (CEHC) levels were significantly higher with γ-Toc intake than with placebo intake. There were no significant between-supplement differences in serum electrolyte levels or cumulative urinary potassium excretion. CONCLUSION: γ-Toc intake could effectively alleviate certain premenstrual syndrome symptoms, particularly those related to water retention during the luteal phase. Furthermore, the underlying mechanism may involve the diuretic effect of γ-CEHC, which is a γ-Toc metabolite. TRIAL REGISTRATION: UMIN000047989; registration date: 10/06/2022, retrospectively registered.

Association between equol producers and type 2 diabetes mellitus among Japanese older adults.

AIMS/INTRODUCTION: Equol, which is produced by enteric bacteria from soybean isoflavones, has a chemical structure similar to estrogen. Both in vivo and in vitro studies have shown the beneficial metabolic effects of equol. However, its effects on type 2 diabetes remain unclear. We investigated the association between the equol producers/non-producers and type 2 diabetes. MATERIALS AND METHODS: The participants included 147 patients with type diabetes mellitus aged 70-89 years, and 147 age- and sex-matched controls. To ascertain the equol producers or non-producers, we used the comparative logarithm between the urinary equol and daidzein concentrations (cut-off value -1.75). RESULTS: The urinary equol concentration was significantly lower in the diabetes group compared with the non-diabetes group (P = 0.01). A significant difference in the proportion of equol producers was observed among all participants (38.8% in the diabetes group and 53.1% in the non-diabetes group; P = 0.01). The proportion of equol producers among women was significantly lower in the diabetes group (31.4%) than in the non-diabetes group (52.8%; P < 0.01). Additionally, the frequency of dyslipidemia in female equol producers was significantly lower than that in female non-equol producers (P < 0.01). Among men, no such differences were observed. We found a significant positive correlation between the urinary equol and daidzein concentrations among equol producers (r = 0.55, P < 0.01). CONCLUSIONS: Our study findings showed that postmenopausal women had a low proportion of equol producers with diabetes and dyslipidemia.

Identification of a novel dihydrodaidzein racemase essential for biosynthesis of equol from daidzein in Lactococcus sp. strain 20-92.

Equol is metabolized from daidzein, a soy isoflavone, by the gut microflora. In this study, we identified a novel dihydrodaidzein racemase (L-DDRC) that is involved in equol biosynthesis in a lactic acid bacterium, Lactococcus sp. strain 20-92, and confirmed that histidine-tagged recombinant L-DDRC (L-DDRC-His) was able to convert both the (R)- and (S)-enantiomers of dihydrodaidzein to the racemate. Moreover, we showed that recombinant L-DDRC-His was essential for in vitro equol production from daidzein by a recombinant enzyme mixture and that efficient in vitro equol production from daidzein was possible using at least four enzymes, including L-DDRC. We also proposed a model of the metabolic pathway from daidzein to equol in Lactococcus strain 20-92.

Comparative activities of the S-enantiomer and racemic forms of equol on bone fragility in ovariectomized mice.

We compared the effects of the S-enantiomer and racemic forms of equol on bone using ovariectomized (OVX) mice. Femoral bone mineral density and bone strength decreased in the OVX mice, but not in OVX mice administered 0.5 mg/d S-equol. This, however, did not hold for racemic equol. Serum and urine S-equol concentrations were higher in the mice administered S-equol than in those administered racemic equol. These results suggest that the inhibitory effects of S-equol on bone fragility in OVX mice are greater than those of racemic equol.

Discovery of an S-equol rich food stinky tofu, a traditional fermented soy product in Taiwan.

A recent epidemiological study showed that daily intake of mg quantities of S-equol is required for health-promoting effects in menopausal women. However, the maximum equol content in food was reported to be approximately 130 µg/100 g in egg yolk. The objective of this study was to find a high equol-containing food. We measured the equol content of 33 egg yolks and 21 fermented soybean foods. Equol was detected in 28 egg yolks at the maximum content of 43 µg/100 g. In the fermented soybean foods, equol was detected only in stinky tofu. We examined 16 stinky tofu samples purchased during different seasons and the average equol content was 1.39 mg/100 g, ranging from 0.34 to 2.68 mg/100 g. Equol was present in stinky tofu as the S-enantiomeric form and as an aglycon type. This is the first report demonstrating that stinky tofu contains high levels of S-equol, which may exert beneficial effects in menopausal women.

Cloning and expression of a novel NADP(H)-dependent daidzein reductase, an enzyme involved in the metabolism of daidzein, from equol-producing Lactococcus strain 20-92.

Equol is a metabolite produced from daidzein by enteric microflora, and it has attracted a great deal of attention because of its protective or ameliorative ability against several sex hormone-dependent diseases (e.g., menopausal disorder and lower bone density), which is more potent than that of other isoflavonoids. We purified a novel NADP(H)-dependent daidzein reductase (L-DZNR) from Lactococcus strain 20-92 (Lactococcus 20-92; S. Uchiyama, T. Ueno, and T. Suzuki, international patent WO2005/000042) that is involved in the metabolism of soy isoflavones and equol production and converts daidzein to dihydrodaidzein. Partial amino acid sequences were determined from purified L-DZNR, and the gene encoding L-DZNR was cloned. The nucleotide sequence of this gene consists of an open reading frame of 1,935 nucleotides, and the deduced amino acid sequence consists of 644 amino acids. L-DZNR contains two cofactor binding motifs and an 4Fe-4S cluster. It was further suggested that L-DZNR was an NAD(H)/NADP(H):flavin oxidoreductase belonging to the old yellow enzyme (OYE) family. Recombinant histidine-tagged L-DZNR was expressed in Escherichia coli. The recombinant protein converted daidzein to (S)-dihydrodaidzein with enantioselectivity. This is the first report of the isolation of an enzyme related to daidzein metabolism and equol production in enteric bacteria.

Daidzein-metabolising phenotypes in relation to serum lipids and uric acid in adults in Guangzhou, China.

Previous studies have suggested that daidzein's metabolites, equol and O-desmethylangolensin (O-DMA), rather than daidzein itself may contribute to the beneficial effects of soya foods in the prevention of CVD. The present study aims to assess the proportion of equol and O-DMA producers, and to compare differences in anthropometric factors, serum lipids, glucose and uric acid between producers and non-producers in Chinese adults aged 20-69 years. For the present cross-sectional study, 202 subjects (100 women and 102 men) were recruited. Twenty-four-hour urinary daidzein and its metabolites were determined in these subjects while on their usual diet and again after a 3-d isoflavone challenge. Fasting serum lipids, glucose and uric acid were examined on their usual diet. Three days of 24 h dietary recalls were used to assess dietary intakes. Of the 202 subjects, 27 (13.4 %) and 27 (13.4 %) excreted equol and O-DMA on their usual diet, and 101 (50 %) and 94 (46.5 %) produced equol and O-DMA after a load of 80 mg/d isoflavones. Equol producers showed lower serum uric acid ( - 10.2 %, P = 0.001), TAG ( - 29.5 %, P = 0.007) and waist:hip ratio ( - 2.6 %, P = 0.032), and tended to have higher HDL cholesterol (6.3 %, P = 0.069) compared with equol non-producers. There were no significant differences in serum lipids, glucose and uric acid between O-DMA producers and non-producers. In conclusion, equol phenotypes might influence cardiovascular risk.

Prevalence of the equol-producer phenotype and its relationship with dietary isoflavone and serum lipids in healthy Chinese adults.

BACKGROUND: Studies have suggested that daidzein-metabolizing phenotypes have beneficial effects on a range of health outcomes. We investigated the prevalence of equol producers and the relationship of equol phenotype with habitual isoflavone consumption and serum lipid concentrations in 200 Chinese adults in Beijing. METHODS: After the baseline survey and dietary records, 200 healthy adults in Beijing were challenged with a soy-isoflavone supplement for 3 days; 24-hour urine samples were collected before and after the challenge. Isoflavones and their metabolites in urine were measured to determine equol phenotype. Serum lipids, uric acid, and other biochemical markers were also measured. RESULTS: Only 26.8% of the participants excreted equol when on a regular diet, as compared with 60.4% after the challenge. After the challenge, urinary isoflavonoid excretion increased in all participants, while equol excretion increased only in equol producers. Isoflavone intake was correlated with urinary isoflavone (range r = 0.49-0.58, P < 0.01). As compared with nonproducers, equol producers were less likely to consume cereals (P < 0.001). There was no significant correlation between serum lipids and isoflavone intake. Serum lipids were not significantly affected by equol phenotype. CONCLUSIONS: Urinary equol excretion was detected in about 25% of participants under their usual dietary conditions. Their potential to produce equol was increased after the challenge. Urinary isoflavone levels may serve as a useful biomarker for isoflavone intake in populations. We observed an association between equol phenotype and cereal intake. Our findings also suggest that dietary isoflavone intake has no significant effect on serum lipids in healthy participants, regardless of equol phenotype.

[Prevalence of equol producer phenotype and its relations to lifestyle factors and dietary intakes among lifestyle factors and dietary intakes among healthy Chinese adults in Beijing].

OBJECTIVE: To investigate the prevalence of equol producers and the physiological range of urinary equol excretion, and also to evaluate relations between equol phenotype and lifestyle among Chinese adults in Beijing. METHODS: 100 male and 100 female adults participated in a cross-sectional study and provided twice 1d urine samples on regular diet and after 3d soy isoflavone challenge respectively. A health and demographics questionnaire, and 2d food record were completed before the urine collections. Isoflavones and their metabolites in urine were measured to determine equol phenotype by HPLC. RESULTS: The physiological range of 24h urinary equol excretion was 0-76.56 micromol/24h, and the percentage of the equol producer phenotype was 26.8% on regular diet and 60.4% after soy isofavone challenge, respectively. There was no indication that habitual consumption of soy foods is associated with the equol producer phenotype. The correlations of isoflavone intake from 2d food record with those from urinary isoflavone levels were 0.58 for total isoflavones, 0.49 for daidzein, 0.56 for genistein, and 0.50 for glycitein (P < 0.01). CONCLUSION: About one fourth of Chinese adults in Beijing were detected equol excretion in urine under the usually lifestyle. However, equol_producing potential was higher.

Optimal cut-off value for equol-producing status in women: The Japan Nurses' Health Study urinary isoflavone concentration survey.

Equol is one of the most active soy isoflavones. When the association between soy food intake in daily life and health outcomes is examined in epidemiological studies, it is important to define the equol-producing status of each individual. However, few studies have assessed equol-producing status without a soy challenge test. To determine a robust cutoff criterion for equol producer classification in observational studies, we conducted a urinary isoflavone concentration survey in daily life among women. Furthermore, we examined the association between eating habits regarding soy foods and equol-producing status. A total of 4,412 participants were included in the analyses. Urinary isoflavones were analyzed using a high-performance liquid chromatography method. We examined the distribution of the log10 equol/daidzein ratios, finding a mixture of two normal distributions, corresponding to equol producer and non-producer subpopulations. Applying a finite mixture model, we estimated the means, standard deviations, and mixing proportions of these two distributions. The estimation was carried out using the SAS NLIN procedure. The optimal cutoff point for the log10 equol/daidzein ratio in the study population was determined to be -1.42, according to the estimated parameters of the mixture distribution. Based on this criterion, 1,830 (41.5%) of the participants were identified as equol producers. Compared with non-consumers of soy foods, consumers of soy foods had significantly higher odds of being equol producers. Using log10-transformed equol/daidzein ratios ≥ -1.42 to define equol producers among Japanese women is reasonable and suitable for determining equol-producing status in epidemiological studies. We found that soy food eating habits were associated with equol-producing status. Further investigation is required to evaluate associations between equol-producing status in daily life and health outcomes. The results of this study suggest the best cutoff point to use in the definition of equol-producing status in daily life.

Possible role of equol status in the effects of isoflavone on bone and fat mass in postmenopausal Japanese women: a double-blind, randomized, controlled trial.

OBJECTIVE: Equol is more biologically active than its precursor daidzein, which is the principal isoflavone found in soybean. There are interindividual differences in the ability to produce equol; these may lead to differences in the effects of isoflavone intervention on human health. This study aimed to investigate whether the effects of soy isoflavones on bone and fat mass are related to an individual's equol status. DESIGN: We performed a 1-year double-blind, randomized trial to compare the effects of isoflavone (75 mg of isoflavone conjugates/day) with those of placebo on bone mineral density, fat mass, and serum isoflavone concentrations in early postmenopausal Japanese women who were classified based on their equol-producer phenotype. RESULTS: After 1 year, the isoflavone intervention significantly increased the serum equol concentration in the equol producers but not in the nonproducers. In the isoflavone group, the annualized changes in the bone mineral density of the total hip and intertrochanteric regions were -0.46% and -0.04%, respectively, in the equol producers and -2.28% and -2.61%, respectively, in the nonproducers; these values were significantly different (P<0.05 for both the regions). Significant differences were observed between the equol producers and nonproducers in the isoflavone group with regard to the annualized changes in the fat mass. No significant difference in the annualized changes in bone mineral density and fat mass was observed between the equol producers and nonproducers in the placebo group. CONCLUSIONS: Our data suggest that the preventive effects of isoflavones on bone loss and fat accumulation in early postmenopausal women depend on an individual's equol-producing capacity.

S-equol Exerts Estradiol-Like Anorectic Action with Minimal Stimulation of Estrogen Receptor-α in Ovariectomized Rats.

Chronic estrogen replacement in ovariectomized rats attenuates food intake and enhances c-Fos expression in the suprachiasmatic nucleus (SCN), specifically during the light phase. S-equol, a metabolite of daidzein, has a strong affinity for estrogen receptor (ER)-ß and exerts estrogenic activity. The purpose of the present study was to elucidate whether S-equol exerts an estrogen-like anorectic effect by modifying the regulation of the circadian feeding rhythm in ovariectomized rats. Ovariectomized female Wistar rats were divided into an estradiol (E2)-replaced group and cholesterol (vehicle; Veh)-treated group. These animals were fed either a standard diet or an S-equol-containing diet for 13 days. Then, the brain, uterus, and pituitary gland were collected along with blood samples. In the rats fed the standard diet, E2 replacement attenuated food intake (P < 0.001) and enhanced c-Fos expression in the SCN (P < 0.01) during the light phase. Dietary S-equol supplementation reduced food intake (P < 0.01) and increased c-Fos expression in the SCN (P < 0.01) in the Veh-treated rats but not in the E2-replaced rats during the light phase. Dietary S-equol did not alter ER-α expression in the medial preoptic area or the arcuate nucleus, nor did dietary S-equol affect pituitary gland weight or endometrial epithelial layer thickness. By contrast, E2 replacement not only markedly decreased ER-α expression in these brain areas (P < 0.001) but also increased both the pituitary gland weight (P < 0.001) and the endometrial epithelial layer thickness (P < 0.001). Thus, dietary S-equol acts as an anorectic by modifying the diurnal feeding pattern in a manner similar to E2 in ovariectomized rats; however, the mechanism of action is not likely to be mediated by ER-α. The data suggest a possibility that dietary S-equol could be an alternative to hormone replacement therapy for the prevention of hyperphagia and obesity with a lower risk of adverse effects induced by ER-α stimulation.

Effects of isoflavone and exercise on BMD and fat mass in postmenopausal Japanese women: a 1-year randomized placebo-controlled trial.

UNLABELLED: The combined intervention of isoflavone intake and walking exercise over 1 year in postmenopausal Japanese women exhibited a trend for a greater effect on prevention of bone loss at the total hip and Ward's triangle regions. INTRODUCTION: The additive effects of isoflavones and exercise on bone and lipid metabolism have been shown in estrogen-deficient animals. In this study, we determined the effects of isoflavone intake, walking exercise, and their interaction on bone, fat mass, and lipid metabolism over 1 year in postmenopausal Japanese women. MATERIALS AND METHODS: A total of 136 postmenopausal women at <5 years after the onset of menopause were randomly assigned to four groups: (1) placebo, (2) walking (45 minutes/day, 3 days/week) with placebo, (3) isoflavone intake (75 mg of isoflavone conjugates/day), and (4) combination of isoflavone plus walking. BMD, fat mass, serum lipid, and serum and urinary isoflavone concentrations were assessed. RESULTS: A significant main effect of isoflavone on the reduction in trunk fat mass was obtained at 12 months. Significant main effects of walking on the reduction in fat mass in the whole body and the trunk were observed at 3, 6, and 12 months and that in the legs and arms at 6 and 12 months. Serum high-density lipoprotein (HDL)-cholesterol concentration significantly increased by 12 months after the walking and the combined intervention. After 12 months, a significant main effect of isoflavone on BMD was observed only at Ward's triangle. Walking prevented bone loss at the total hip and the Ward's triangle to significant degrees. The effect of the combined intervention on BMD at total hip and Ward's triangle regions was greater than that of either alone. No significant interaction was observed between isoflavone and walking in any measurements recorded during the study. CONCLUSIONS: Our study suggest that combined intervention of 75 mg/day of isoflavone intake and walking exercise 3 times/week for 1 year showed a trend for a greater effect on BMD at total hip and Ward's triangle regions than either alone. Intervention with isoflavone in postmenopausal Japanese women showed a modest effect on BMD compared with those in Westerners. Further studies over longer treatment duration that include assessment of BMD at various regions are necessary to ascertain the clinical significance of the combined intervention of isoflavone plus walking in postmenopausal women.

Cooperative effects of isoflavones and exercise on bone and lipid metabolism in postmenopausal Japanese women: a randomized placebo-controlled trial.

Cooperative effects of isoflavones and exercise on bone and lipid metabolism have been exhibited in estrogen-deficient animals; however, results from clinical trials have not been published. In this study, we determined the effects of isoflavone intake and walking and their interaction on bone and lipid metabolism in postmenopausal women over 24 weeks. The bioavailability and metabolism of isoflavones (daidzein in particular) were also examined to clarify the mechanism of their bone-protective effects in humans. One hundred twenty-eight subjects were randomly assigned to 4 groups: placebo; placebo combined with walking (3 times per week); isoflavone intake (75 mg of isoflavones conjugates per day); and isoflavone combined with walking. The subjects were classified by equol status (producers or nonproducers) as identified using production of equol from daidzein in fecal culture. Bone mineral density (BMD), body composition, and serum concentrations of isoflavones were assessed. Serum high-density lipoprotein cholesterol concentration significantly increased (6.1%, P = .03), and fat mass in the whole body significantly decreased (-4.3%, P = .0003) from the baseline in the combined intervention group. There were no significant differences in BMD between baseline and postintervention in any of the treatment groups. However, the percent changes in BMD in equol producers were -0.53% and +0.13% in the sub-whole body and total hip, respectively. This was significantly different compared with -1.35 and -1.77 for the sub-whole body and total hip, respectively, in nonproducers in the isoflavone group (P = .049 and .040, respectively). The mean serum equol concentration was significantly higher in equol producers than in nonproducers in the isoflavone groups, but not in the placebo group. The combination of isoflavones and exercise exhibited favorable effects on serum lipid and body composition of postmenopausal women. The findings of this study suggest that the preventive effects of isoflavones on bone loss depend on the individual's intestinal flora for equol production.